The association between corticosteroid treatment and gastric ulcer healing is controversial. The effects ofcorticosteroids on experimental ulcer healing in the rat were studied and the effect of coadministration of a prostaglandin E1 analogue was determined. Forty male adult rats were divided into five groups and pretreated for 10 days as follows: (a) control, (b) prednisolone (10 mg/kg), (c) analysis of prospective studies of adrenocorticosteroid and adrenocorticotrophic hormone therapy, Conn and Blitzer1 concluded that overall the frequency ofpeptic ulcer was not noticeably increased during therapy, although upper gastrointestinal haemorrhage was more common in patients taking corticosteroids. In addition, peptic ulcer appeared to be more common in patients who had received a large total dose of prednisolone (>1000 mg) and those who had been treated for more than 30 days. More recently, Messer et al 2 re-examined the association between corticosteroid therapy and peptic ulceration or gastrointestinal haemorrhage in 71 controlled clinical trials. They concluded that there was an increased risk of peptic ulceration (relative risk 2.3, 95% confident interval 1.4, 3.7) and haemorrhage in patients taking corticosteroids.These observations result in hypotheses about the mechanism of the increased incidence and complication rates of peptic ulcers and also call for strategies to prevent ulcer development and enhance healing. Our recent studies have shown that non-steroidal antiinflammatory drugs (NSAIDs), another class of drugs commonly associated with gastroduodenal complications, depress the processes of epithelial cell proliferation that leads to ulcer healing. The coadministration of a prostaglandin E1 analogue (PGE1), however, returned to normal the rates of experimental ulcer healing and of cell proliferation in the proliferative compartment of the gastric crypts adjacent to the ulcer edge.3We examined the theory that the healing of ulcers would be slowed by corticosteroid therapy, and investigated the effect of this treatment on both ulcer size and the rate of regenerative repair at the ulcer edge in gastric ulcers induced by cryoprobe in the rat stomach. In addition, we studied the effect of the PGE1 analogue misoprostol on ulcer healing in rats given corticosteroids. For comparison we included a group of animals treated with indomethacin, a known inhibitor of regenerative repair at the edges of cryoulcers.Studies of cell proliferation during ulcer healing have generally measured DNA synthesis by methods such as [3H]-thymidine labelling followed by autoradiography, or immunohistochemistry for the incorporated uridine analogue 5-bromo-2-iododeoxyuridine (BrdU). Although these methods are accurate, they are time consuming and cumbersome. Proliferating cell nuclear antigen (PCNA) is a nuclear protein that is expressed maximally at the time of the 'S' phase and can be used to identify proliferating cells by immunostaining. It has the advantage of being detectable in formalin fixed paraffin sections. We a...

Fluticasone propionate, a topicaily active

No abstract

Localisation and quantification of protein loss in protein-losing enteropathy (PLE) is useful in the clinical management of hypoalbuminaemia. Indium-111 transferrin offers the opportunity of combining localisation and quantification using a single agent. Twenty-five studies were performed in 23 patients with suspected PLE: 111In-transferrin was prepared by incubating autologous cell-free plasma with 111In chloride in vitro for 15 min. Protein loss was quantified by comparing whole-body counts recorded with an uncollimated gamma camera at 3 h and 5 or 6 days after injection of 111In-transferrin. Gamma camera imaging performed at 3 and 24 h after injection demonstrated a site of protein loss in 15 studies. Whole-body 111In excretion was abnormally elevated in 13 of these, ranging from 16% to 34% (normal <10%), was not assessed in one and was less than 10% in a patient with carcinoid syndrome. In the ten studies that were negative on imaging, whole-body 111In excretion was normal in nine and elevated at 22% in a further patient with carcinoid syndrome. Overall, the mean whole-body 111In excretion in studies with positive imaging was 21.4% (SD 6.1%) (n=14), significantly higher (P<0.01) than in studies with negative imaging, in which it was 7.5% (SD 6.7%) (n=10). This technique should be useful for the combined approach of localising and quantifying protein loss in PLE.

Although effective for both acute and often long term treatment of inflammatory bowel disease, systemically absorbed corticosteroids have a high incidence of side effects. This article briefly reviews the pharmacokinetics of corticosteroids and the strategics available for reducing systemic side effect~. In rarricular, fluttcasone propionate is a fluorinated glucocorticoid, in which systemic side effects are absent or minimal due to its relatively low absorption and rapu.l first pass metabolism In an open trial in 12 patients with mild and moderately active Crohn's disease, administration of 20 mg fluttcasone pro1,1onate or.1lly was associated with a significant fall in the Crohn's disease activity index and improvement in other parameters of inflammation, without change in either plasma cortisol levels or responsiveness to adrenocorticotropic hormone, suggesting that this drug is a promising therapy fo r Crohn's disease meriting evaluation against conventional corticosteroids. Can J Gastroenterol 1990;4(7):417-419 Key Words: CLnica! tnal, Corticosteroids, Crohn's disease, Fluticasone propionate Le propionate de fluticasone dans les maladies inflammatoires de l'intestin RESUME: Bien qu'efficaces dans le traitemcnt des maladies inflammatoires de l'intestin -aigues et a long terme, !es corticostero"ides absorbes par voie genera le s'accompagnent d'une incidence elevee d'effets indesirables. Le present article examine rapidement la pharmacocinetique des comcostero"ides ainsi que les strategies permettant de redu ire les effets secondaires systemiques. ll note que le propionate de fluticasone est un glucocortico"ide fluore dont les effets sccondaires sont absents ou minimes en raison de son absorption foible et de son metabolisme rapide de premier passage. Dans un cssai ouvert, 12 patients portcurs d'une maladie de Crohn faiblement ou mcxic'.:rement active ont re~u du propionate de fluticasone oral a la dose de 20 mg. Les resultats -chute significative du CDAI et amelioration des paramecrcs inflammatoires, sans changement des taux plasmatiques de cortisol ou de la reponse a l'ACTH -suggerent que ce medicament pourra1t offrir un remede prometteur a la maladie de Crohn et qu'il merite d'etre evalue par rapport aux corticostero"ides conventionnels.